PB1751: ALTERATIONS IN THE GUT MICROBIOME IN PEDIATRIC, ADOLESCENT, AND YOUNG ADULT PATIENTS WITH ACUTE LEUKEMIA
Authors: M. Park, J. Jung, H.-Y. Jin, J. A. Lee, E. Lee, H. Lee, H. S. Eom, H. J. Park
Journal: HemaSphere (2022)

Background: Gut microbiome is involved in the progression of various diseases and may affect the human immune system. The composition of gut microbiome and its change upon anti-leukemic therapy in pediatric, adolescent, and young adult patients with acute leukemia is poorly understood. Aims: We performed a longitudinal analysis of gut microbiome composition to assess associations between gut microbial dynamics and clinical outcomes in pediatric, adolescent, and young adult patients with acute leukemia during chemotherapy and/or hematopoietic cell transplantation (HCT). And also, we aimed to compare the gut microbiome composition of leukemia patients with their healthy sibling controls. Methods: The bacterial 16S rRNA gene was analyzed by high-depth sequencing to determine the diversity and composition of the microbiome. Data collected between August 2020 and September 2021. The median age of patients was 17.1 years (range from 3.5 years to 34.1 years). Seventy-nine stool samples from 15 patients (10 acute lymphoblastic leukemia and 5 acute myeloid leukemia) and 9 stool samples from 9 siblings were analyzed in this study. Relative abundance, overall richness, various diversity indexes were calculated. Results: At diagnosis, microbial diversity index of the patient group was lower than that of their siblings. Clostridia and Lachnospiraceae were reduced in patients, but Actinobacteria were more abundant in patients compared to sibling controls. The Firmicutes/Bacteroidetes (F/B) ratio was not different between patients and their siblings. In patients, microbial diversity decreased after induction chemotherapy, but it recovered to a level similar to that of sibling controls after consolidation chemotherapy. The F/B ratio significantly increased after induction, but it decreased to a similar value at diagnosis after consolidation. Microbial diversity index at diagnosis was significantly lower in patients who experienced fever and/or infection during induction compared to patients who did not. A baseline abundance of Proteobacteria predicted fever and/or infection during induction chemotherapy. In patients underwent HCT, compared to the values before HCT, the number of identified species has decreased to about half at day 28 after HCT and decreased further at day 56 after HCT. However, it recovered to pre-HCT level at day 90 after HCT. Diversity index significantly decreased at day 0 of HCT compared to that of pre-HCT, but it recovered to a level similar to that of pre-HCT at day 90 after HCT. At day 0 of HCT, patients who experienced fever and/or acute graft versus host disease (aGVHD) within day 100 of HCT showed abundant Bacteroidetes with median F/B ratio of 0.1, while patients who did not showed low level of Bacteriodetes with median F/B ratio of 1.4. Diversity index at day 0 of HCT was not different between patients who experienced fever and/or aGVHD and patients who did not. Summary/Conclusion: In pediatric, adolescent, and young adult patients undergoing therapy for acute leukemia, decreased microbial diversity and abundance of Proteobacteria at diagnosis were associated with fever and/or infection during induction chemotherapy. Abundance of Bacteroidetes at day 0 of HCT predicted subsequent fever and/or acute GVHD. Better understanding of the gut microbiome could provide actionable information in guiding precision medicine.